School of Life Sciences, Tsinghua University, Beijing, 100084, P.R. China.
Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, P.R. China.
Sci Rep. 2020 Feb 6;10(1):2044. doi: 10.1038/s41598-020-58729-6.
GPNCA is a long non-coding RNA with unknown functions. In this study, using data from 9 cancers obtained from The Cancer Genome Atlas (TCGA), GPNCA was identified as overexpressed in cancer vs. normal tissues. The upregulation of GPNCA was associated with poor overall prognosis in colon, liver, renal clear cell and breast cancers. The upregulation of GPNCA was partly due to enhanced H3K27ac occupancy on its promoter region via EP300 and KAT2A/GCN5. The overexpression of GPNCA was positively related to tumor metastasis in colon cancer and poor disease-free and recurrence-free survival in colon and liver cancer. Both gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that GPNCA was closely linked to regulation of gene transcription and post-transcriptional modifications, which was further supported by in vitro cell cytoplasmic and nuclear RNA purification assessments. Furthermore, GPNCA was associated with cell growth. Our in vitro experiments demonstrated that GPNCA silencing inhibited tumor growth via inhibiting its nearby gene GSK3B. Taken together, these findings highlight GPNCA as a biomarker for cancer diagnosis and a potential target for future cancer drug development.
GPNCA 是一种具有未知功能的长非编码 RNA。在这项研究中，利用来自癌症基因组图谱（TCGA）的 9 种癌症的数据，发现 GPNCA 在癌症与正常组织中的表达上调。GPNCA 的上调与结肠癌、肝癌、肾透明细胞癌和乳腺癌的总体预后不良相关。GPNCA 的上调部分归因于通过 EP300 和 KAT2A/GCN5 增强其启动子区域的 H3K27ac 占有率。GPNCA 的过表达与结肠癌的肿瘤转移呈正相关，与结肠癌和肝癌的无病生存期和无复发生存期不良相关。基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析均表明，GPNCA 与基因转录和转录后修饰的调控密切相关，体外细胞质和核 RNA 纯化评估进一步支持了这一点。此外，GPNCA 与细胞生长有关。我们的体外实验表明，通过抑制其附近基因 GSK3B，GPNCA 的沉默抑制了肿瘤的生长。总之，这些发现强调了 GPNCA 作为癌症诊断的生物标志物和未来癌症药物开发的潜在靶点。
